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https://hdl.handle.net/2440/97493
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Type: | Journal article |
Title: | New insights into lineage restriction of mammary gland epithelium using parity-identified mammary epithelial cells |
Author: | Chang, T. Kunasegaran, K. Tarulli, G. De Silva, D. Voorhoeve, P. Pietersen, A. |
Citation: | Breast Cancer Research, 2014; 16(1):R1-1-R1-16 |
Publisher: | BioMed Central |
Issue Date: | 2014 |
ISSN: | 1465-5411 1465-542X |
Statement of Responsibility: | Ted H-T Chang, Kamini Kunasegaran, Gerard A Tarulli, Duvini De Silva, P Mathijs Voorhoeve, and Alexandra M Pietersen |
Abstract: | INTRODUCTION: Parity-identified mammary epithelial cells (PI-MECs) are an interesting cellular subset because they survive involution and are a presumptive target for transformation by human epidermal growth factor receptor 2 (HER2)/neu in mammary tumors. Depending on the type of assay, PI-MECs have been designated lobule-restricted progenitors or multipotent stem/progenitor cells. PI-MECs were reported to be part of the basal population of mammary epithelium based on flow cytometry. We investigated the cellular identity and lineage potential of PI-MECs in intact mammary glands. METHODS: We performed a quantitative and qualitative analysis of the contribution of PI-MECs to mammary epithelial cell lineages in pregnant and involuted mammary glands by immunohistochemistry, fluorescence-activated cells sorting (FACS), and quantitative polymerase chain reaction. PI-MECs were labeled by the activation of Whey Acidic Protein (WAP)-Cre during pregnancy that results in permanent expression of yellow fluorescent protein. RESULTS: After involution, PI-MECs are present exclusively in the luminal layer of mammary ducts. During pregnancy, PI-MECs contribute to the luminal layer but not the basal layer of alveolar lobules. Strikingly, whereas all luminal estrogen receptor (ER)-negative cells in an alveolus can be derived from PI-MECs, the alveolar ER-positive cells are unlabeled and reminiscent of Notch2-traced L cells. Notably, we observed a significant population of unlabeled alveolar progenitors that resemble PI-MECs based on transcriptional and histological analysis. CONCLUSIONS: Our demonstration that PI-MECs are luminal cells underscores that not only basal cells display multi-lineage potential in transplantation assays. However, the lineage potential of PI-MECs in unperturbed mammary glands is remarkably restricted to luminal ER-negative cells of the secretory alveolar lineage. The identification of an unlabeled but functionally similar population of luminal alveolar progenitor cells raises the question of whether PI-MECs are a unique population or the result of stochastic labeling. Interestingly, even when all luminal ER-negative cells of an alveolus are PI-MEC-derived, the basal cells and hormone-sensing cells are derived from a different source, indicating that cooperative outgrowth of cells from different lineages is common in alveologenesis. |
Keywords: | Mammary Glands, Animal Epithelial Cells Multipotent Stem Cells Animals Mice, Transgenic Mice Bacterial Proteins Milk Proteins Caseins DNA-Binding Proteins Luminescent Proteins Integrin alpha6 Receptors, Estrogen Transcription Factors Flow Cytometry Parity Cell Differentiation Cell Lineage Pregnancy Female Antigens, CD24 |
Rights: | © 2014 Chang et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
DOI: | 10.1186/bcr3593 |
Published version: | http://dx.doi.org/10.1186/bcr3593 |
Appears in Collections: | Aurora harvest 7 Medicine publications |
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hdl_97493.pdf | Published version | 4.39 MB | Adobe PDF | View/Open |
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